The present invention is related to a biocompatible porous hollow fiber made of a polyolefine material and having a coating of a biocompatible carbon material. In the present context "biocompatible" means especially excellent compatibility with respect to blood and tissue; in so far biocompatibility includes haemo compatibility and thromboresistance. The biocompatible porous hollow fiber according to the present invention is especially suited for providing exchange materials, diaphragmas and/or semipermeable membranes within devices, which will contact blood or plasma outside the living body, such as in oxygenators, haemo concentrators, dialyzer apparatuses, haemo filter devices and the like, and for providing surfaces which will contact blood and/or plasma and in other equipments for maintaining an extracorporal circulation of blood and/or plasma.
Further, the present invention is related to a method of manufacturing said biocompatible porous hollow fiber. Further, the present invention is related to specific kinds of use of said biocompatible porous hollow fiber, especially for providing exchange materials, diaphragmas and/or semipermeable membranes in oxygenators, dialyzer apparatuses, haemo concentrators, haemo filters and other components of an extracorporal blood circulation.
Microporous open-celled hollow fibers are well known in the art. An especially important application concerns the use as exchange materials or as intermediate product for providing exchange materials, diaphragmas and/or semipermeable membranes for effecting a gas exchange, for example in oxygenators, for purposes of filtration, ultra-filtration and micro-filtration, for example in blood filter devices, in dialyzer apparatuses, for effecting a reverse osmosis, for effecting a heat exchange and the like. A degree of porosity and the number, form and dimensions of pores will be matched to the specific kind of use. Typically, the porosity may range of from 10 to 50%, and the pores may comprise a dimension, especially a diameter less than one micron. In these fields of use, the hollow fiber wall will typically contact blood and/or plasma. Commonly used hollow fiber materials include polyester, polyethylene and especially polypropylene.
In general, two different methods are available for preparing microporous open-celled hollow fibers consisting of polypropylene. According to a first alternative, non-drawn hollow fibers will be substantially drawn at a temperature lower than 110.degree. C. This kind of drawing provides porous areas being oriented vertically to the drawing direction. A method of this type is disclosed in German patent specification No. 26 30 374. According to a further proposal of said kind, a hot-drawing step may be effected subsequently to the cold-drawing step, as disclosed in German Offenlegungsschrift No. 30 03 400. According to another, second alternative, a homogenous one-phase mixture is provided comprising a fiber-forming polymer such as polypropylene and further comprising an additional liquid phase being inert with respect to the fiber-forming polymer. This two-component mixture is extruded into a bath, wherein the formed hollow fiber will solidify. Thereafter, the hollow fiber is treated with a solvent in order to dissolve and remove the liquid phase.
This removal of the liquid phase generates pores and micropores within the hollow fiber wall. This method is disclosed in German patent specification No. 28 33 493. According to a modified version of this method, micro-porous hollow fibers may be obtained which consist of polyethylene, as disclosed in German patent specification No. 27 18 155.
In the present context "biocompatible" or "biocompatibility" describes the mutual effects of the polymer fiber material with blood and/or plasma. Natural active blood forms a living system of cells, factors and proteines which act rather aggressively upon foreign surfaces. A contact of blood with such foreign surfaces may cause a haemolysis which decreases the number of active erythrocytes yielding in a reduced capacity of oxygen take-off and oxygen transportation. In order to overcome this defect, a higher oxygen partial pressure has to be provided within an extra-corporal circulation system, which may enhance the haemolysis. Further, leukocytes may be deposited on the fiber surface; subsequently to an operation, those deposited leukocytes are missing, and the decreased number of leukocytes in the blood of a patient increases a danger of post-operative infection.
Further, the fiber surface may activate the so called complement complex which effects the immuno system and the blood factors. Finally, the fiber surface may activate the blood coagulation cascade including a fibrinogenesis until the formation and deposition of fibrin clots and thrombi. Therefore, the fiber surface shall comprise a biocompatibility as high as possible in order to inhibit or completely hinder an activation of the fore-mentioned processes. Especially, the fiber surface shall comprise a high haemo compatibility and a low tendency for thrombus forming (anti-thrombogenity).
Among the actually available biocompatible materials, pyrolytic carbon seems to be one of the materials comprising the best biocompatible characteristics. Typically, the pyrolysis of carbon containing starting materials and depositing the so formed particulate pyrolytic carbon on a substrate requires high temperatures in the range of from 800.degree. to 1000.degree. C. and more. Medical prosthetic devices comprising a coating of pyrolytic carbon and methods of manufacture are disclosed in the U.S. Pat. Nos. 4,164,045 or 3,952,334 or 3,685,059 or 3,526,005. The common substrate materials, especially materials based on organic polymers, will be irreversibly impaired by such high temperatures. The European Patent Specification EP 0 224 080 B1 and the U.S. Pat. No. 5,370,684 disclose a method of manufacture a prosthetic device, comprising a substrate made of an organic polymer ("DACRON", "TEFLON") and having a coating of biocompatible carbon material. For example, a coated DACRON yarn is described in said patent which may be used as suture yarn. The coating has been deposited on said yarn at relatively low temperatures by sputtering a carbon target at a given voltage and current. The thus obtained coating comprises a thickness less than 1.0 micron. The thus obtained carbon material is said to consist of turbostratic carbon. The known method is complex and expensive and provides a relatively low productivity.
In case of an improper contact, the extremely thin carbon layer may easily be stripped off from the yarn or from other substrates.
Typically, oxygenators, dialyzers, blood filters, haemo concentrators and similar devices are intended and designed for a one-time use. Typically those devices comprise more than 1 m.sup.2 exchange surface which is based on porous hollow fibers. Therefore, porous hollow fibers of said kind are required and used in large quantities. The fore-mentioned low temperature sputtering process is too expensive in order to coat large quantities of hollow fibers with pyrolytic or turbostratic carbon according to said process.
According to other proposals, for example British Patents 856,329 or 801,531, the characteristics of polymer substrates may be modified and/or improved by grafting a coating on the surface of said substrates. The grafted polymer layer may be obtained by means of a radicalic graft polymerisation reaction starting from ethylenic unsaturated monomers. The radicalic graft polymerization reaction may be induced by ionizing radiation. A typical ethylenic unsaturated monomer is methyl acrylate. An extended list of other suited monomers includes vinylidene chloride. By means of said grafted coating, a number of different characteristics may be obtained or improved; however, the preparation of a coating comprising biocompatible characteristics is not stated. When grafting within a liquid phase, there is a danger of covering and closing the fine and ultra-fine pores of a porous hollow fiber.
Contrary thereto, there is a still existing demand for a relatively simple method of preparing in high productivity a biocompatible porous hollow fiber comprising a biocompatible carbon material which is chemically bound to the surface of a porous hollow fiber without substantially decreasing or eliminating the porosity of said hollow fiber.